The Food and Drug Administration is about to make one of its most divisive rulings in years, deciding on the destiny of an Alzheimer’s drug that might be the first therapy licensed after almost two decades of unsuccessful attempts to discover a cure for the crippling illness.
On Monday, the FDA will make a decision on aducanumab, a medicine that tries to reduce the growth of memory and cognitive impairments in Alzheimer’s patients early in the illness. If authorized, it would be the first novel Alzheimer’s drug since 2003, as well as the first therapy to target the disease process rather than simply the symptoms.
Analysts expect it will become a blockbuster medicine in a few years, costing tens of thousands of dollars per patient yearly and providing a windfall to Biogen, the manufacturer.
Patient groups are fighting for approval because they are desperate for remedies. However, approving the medicine would go against the advice of numerous notable Alzheimer’s specialists as well as the FDA’s independent advisory committee.
The committee’s majority voted against recommending approval in November, claiming that evidence did not show that aducanumab decreased cognitive deterioration convincingly. Three members of the advisory group then issued a detailed review of the evidence. Other academics, as well as an independent group, believe that aducanumab’s benefits do not exceed its hazards.
“This should not be approved, because substantial evidence of effectiveness hasn’t been shown,” said Dr. Lon Schneider, director of the California Alzheimer’s Disease Center at the University of Southern California and one of many site investigators who helped conduct one of the aducanumab trials. “There’s very little potential that this will address the needs of patients.”
Beyond the status of this specific treatment, some scientists are concerned that approval would decrease criteria for future medications, which is an especially pressing concern at a time when public faith in science is at an all-time low.
“I simply don’t see a path for approval because of the absence of evidence that’s been shared to date that this product works, and I think it would set a remarkably dangerous precedent — not only for the field of Alzheimer’s research but also for the broader regulation of prescription drugs in our country,” said Dr. G. Caleb Alexander, an F.D.A. advisory committee member and an internist, epidemiologist and drug safety and effectiveness expert at the Johns Hopkins Bloomberg School of Public Health.
Officials from Biogen declined to comment for this piece, although they have said that the research indicates cognitive improvement in earnings calls, medical meetings, and FDA presentations. A number of Alzheimer’s experts, including several who have worked with Biogen, have stated that aducanumab “achieves the standard of meaningful efficacy with adequate safety.”
“There’s lots of issues with the data,” said Maria Carrillo, chief science officer for the Alzheimer’s Association, a patient advocacy group that is pushing hard for certification. However, she stated that her group must “weigh the crushing reality of what people live with today” and support giving patients something to try rather than waiting for unequivocal good outcomes after several years.
Alzheimer’s disease affects around six million individuals in the United States and nearly 30 million people worldwide, with the number anticipated to quadruple by 2050. In various stages of Alzheimer’s disease, five drugs now licensed in the United States might slow cognitive deterioration for many months. Around two million people in the United States have moderate Alzheimer’s disease, which qualifies them for aducanumab, a monthly intravenous injection that requires routine imaging to identify possible brain swelling.
The Food and Drug Administration (FDA) normally adopts advisory committee recommendations and requires two persuasive studies for approval, although it has allowed exceptions, particularly for serious conditions with no therapies.
Dr. Ronald Petersen, head of the Mayo Clinic’s Alzheimer’s Disease Research Center in Rochester, Minnesota, says he’s “on the fence.” He said he’d want to provide a new alternative to patients shortly, but “the data are iffy.”
Aducanumab is a monoclonal antibody that targets amyloid, a molecule that accumulates into plaques in Alzheimer’s patients’ brains. Many amyloid-reducing medications have failed to decrease symptoms in clinical trials, according to some experts, making aducanumab’s result all the more crucial. If successful, it would back up a long-held but untested hypothesis that tackling amyloid early in the disease process might be an effective Alzheimer’s treatment.
Acuranumab sparked interest following an early trial that revealed amyloid reduction and suggested it might halt cognitive deterioration. The Food and Drug Administration (FDA) permitted Biogen to bypass Phase 2 studies and perform two Phase 3 studies with 1,640 patients each, which several experts questioned.
Both studies were terminated early in March 2019, after an independent data monitoring committee determined that aducanumab was not functioning. As a result, 37% of individuals did not finish the 78-week trials.
However, in October of that year, Biogen claimed that it had discovered a benefit in one experiment after analyzing data from 318 people who completed the trials before they were terminated but after the results cutoff point set by the monitoring committee. According to Biogen, the highest dose reduced cognitive decline by 22%, or four months, over the course of 18 months in that experiment.
“One study was positive, and one identically performed study was negative,” said Dr. David Knopman, a clinical neurologist at the Mayo Clinic and a site principal investigator for one trial. “I don’t think it takes a Ph.D. in statistics to see that that’s inconclusive.”
Dr. Stephen Salloway, who served as the principle investigator of an aducanumab trial site, described himself as a “passionate” proponent of approval. Because Alzheimer’s disease is so devastating, he believes the evidence is adequate.
“I understand people’s concerns — the data set has issues, of course,” said Dr. Salloway, director of neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I. “F.D.A. is in a tough spot, obviously.”